Rosiglitazone is an oral antidiabetic agent which acts primarily by increasing insulin sensitivity. Chemically, rosiglitazone maleate is (±)-5-[[4-[2-(methyl-2-pyridinylamino) ethoxy]phenyl]methyl]-2,4-thiazolidinedione, (Z)-2-butenedioate (1:1) with a molecular weight of 473.52 (357.44 free base). The molecule has a single chiral center and is present as a racemate. Due to rapid interconversion, the enantiomers are functionally indistinguishable. (Physicians' Desk Reference (electronic version), Thomson Micromedex, Greenwood Village, Colo. (Edition expires [12/05])).
The structural formula of Rosiglitazone Maleate is:

Rosiglitazone Maleate is marketed in the United States under the trade name AVANDIA® in 2 mg, 4 mg, and 8 mg tablets. In addition, Rosiglitazone Maleate in combination with Metformin HCl under the trade name AVANDAMET® in tablets with the following dosages: 1 mg/500 mg; 2 mg/500 mg; 4 mg/500 mg; 2 mg/1000 mg; 4 mg/1000 mg.
Rosiglitazone and its maleate salt are disclosed in the following United States patents, hereby incorporated by reference: U.S. Pat. Nos. 5,002,953; 5,741,803; 6,288,095.
Pharmaceutical products are regulated in most countries by governmental agencies. For example, the U.S. Food & Drug Administration (FDA) generally requires an applicant to show safety and efficacy of the pharmaceutical product during the approval/review phase and requires monitoring of the safety of the drug post-approval.
In order to satisfy safety concerns, the regulatory agencies generally require a manufacturing specification that sets the maximum amount of each identified impurity as well as the maximum amount for all remaining unidentified impurities. In addition, stability testing is performed on the pharmaceutical composition to insure that it does not substantially change over time.
Described herein is an impurity associated with rosiglitazone maleate, along with methods and formulations for minimizing the impurity.